The novel HLA-DPA1*02:117 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-DPA1*02:117 differs from HLA-DPA1*02:02:02:01 by one nucleotide in exon 2.

The discovery of three-dimensional Van Hove singularity.

Arising from the extreme/saddle point in electronic bands, Van Hove singularity (VHS) manifests divergent density of states (DOS) and induces various new states of matter such as unconventional superconductivity. VHS is believed to exist in one and two dimensions, but rarely found in three dimension (3D). Here, we report the discovery of 3D VHS in a topological magnet EuCd2As2 by magneto-infrared spectroscopy. External magnetic fields effectively control the exchange interaction in EuCd2As2, and shift 3D Weyl bands continuously, leading to the modification of Fermi velocity and energy dispersion. Above the critical field, the 3D VHS forms and is evidenced by the abrupt emergence of inter-band transitions, which can be quantitatively described by the minimal model of Weyl semimetals. Three additional optical transitions are further predicted theoretically and verified in magneto-near-infrared spectra. Our results pave the way to exploring VHS in 3D systems and uncovering the coordination between electronic correlation and the topological phase.

Benefit of endovascular treatment for primary versus secondary medium vessel occlusion: A multi-center experience.

AIMS: This study aimed to compare the clinical outcomes and safety of endovascular treatment (EVT) in patients with primary versus secondary medium vessel occlusion (MeVO). METHODS: From the endovascular treatment for acute ischemic stroke in the China registry, we collected consecutive patients with MeVO who received EVT. The primary endpoint was a good outcome, defined as a modified Rankin Scale (mRS) 0 to 2 at 90 days. RESULTS: 154 patients were enrolled in the final analysis, including 74 primary MeVO and 80 secondary MeVO. A good outcome at 90 days was achieved in 42 (56.8%) patients with primary MeVO and 33 (41.3%) patients with secondary MeVO. There was a higher probability of good outcomes in patients with the primary vs secondary MeVO (adjusted odds ratio, 2.16; 95% confidence interval, 1.04 to 4.46; p = 0.04). There were no significant differences in secondary and safety outcomes between MeVO groups. In the multivariable analysis, baseline ASPECTS (p = 0.001), final modified thrombolysis in cerebral infarction score (p = 0.01), and any ICH (p = 0.03) were significantly associated with good outcomes in primary MeVO patients, while baseline National Institutes of Health Stroke Scale (p = 0.002), groin puncture to recanalization time (p = 0.02), and early neurological improvement (p < 0.001) were factors associated with good outcome in secondary MeVO patients. CONCLUSION: In MeVO patients who received EVT, there was a higher likelihood of poor outcomes in patients with secondary versus primary MeVO.

Evaluation of Left Ventricular Function in Patients With Severe Aortic Stenosis Utilizing Automated Cardiac Motion Quantitation Techniques.

OBJECTIVE: The objective of this study is to explore the patterns of alteration in left ventricular systolic function among patients with severe aortic stenosis (SAS) through the application of automatic myocardial motion quantification (aCMQ) techniques. Furthermore, we seek to ascertain dependable quantitative markers for the assessment of impaired left ventricular function in patients with SAS and an ejection fraction (EF) ≥ 60%. METHODS: Seventy patients who underwent echocardiography and received a diagnosis of severe aortic stenosis (SAS) in the hospital from November 2021 to August 2022 were selected for the SAS group and categorized into three subgroups based on ejection fraction (EF)-SAS group with EF ≥ 60%, SAS group with EF ranging from 50% to 59%, and SAS group with EF < 50%. Concurrently, 30 healthy individuals were recruited at the hospital during the same timeframe to serve as the control group. Participants from both groups underwent standard transthoracic echocardiography to assess conventional echocardiographic parameters. Dynamic images were examined using automatic myocardial motion quantification (aCMQ) software to derive longitudinal peak strain (LPS) parameters, which were then subjected to statistical analysis. RESULTS: In comparison to the control group participants, the measurements of ascending aorta diameter (AoD), left atrium diameter (LAD), interventricular septal end diastolic thickness (IVSd), left ventricular posterior wall end diastolic thickness (LVPWd), peak systolic velocity (Vmax), and mean pressure gradient (MPG) were significantly higher in the SAS groups (p < 0.05). When compared to participants in the SAS group with an EF ≥ 60%, the values of IVSd, LVPWd, Vmax, and MPG in the SAS group with EF ranging from 50% to 59% were significantly elevated (p < 0.05). Similarly, left ventricular end-diastolic diameter (LVEDD), the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular velocity (E/e'), and the ratio of early to late diastolic mitral inflow velocities (E/A) in the SAS group with EF < 50% were significantly elevated (p < 0.05). The absolute values of longitudinal peak strain (LPS) in the SAS groups were significantly lower in comparison to those in the control group (p < 0.05). Furthermore, all measurements of left ventricular global longitudinal systolic peak strain (GLPS) showed a positive correlation with MPG, a moderate negative correlation with aortic valve area index (AVAI), and a moderate positive correlation with E/A. CONCLUSIONS: Patients with SAS and an EF < 50% exhibited the most profound impairment in left ventricular myocardial function. Utilizing the aCMQ technique enables the precise and quantitative evaluation of the severity of impaired left ventricular systolic function in patients within the SAS group with an EF ≥ 60%.

Steroidal Saponins from Water Eggplant (Fruits of Solanum torvum) Exhibit Anti-Epileptic Activity against Pentylenetetrazole-Induced Seizure Model in Zebrafish.

The fruits of Solanum torvum Swartz, a wild relative of eggplant, are consumed as a wild vegetable in tropical regions of Africa, Asia, and South America. In traditional Chinese medicine, it is believed to have anti-inflammatory and sedative effects. In the Philippines, water decoction is used to treat hyperactivity disorder. Twenty-two steroidal saponins were isolated and purified from the fruits grown in Yunnan, China, including six new compounds: torvosides U-Z (1-6). During drying and cooking, the saponins may undergo transformation, resulting in small amounts of sapogenins. These transformations can include dehydration of hydroxyl groups at position C22, formation of double bonds at position 20, 22 or 22, 23, and even formation of peroxide products. Saponin compounds torvoside X (4), torvoside Y (5), torvoside A (7), and (25S)-3-oxo-5α-spirostan-6α-yl-O-ß-d-xylopyranoside (20), which are glycosylated at C-6, showed certain anti-epileptic activity in a pentylenetetrazole-induced zebrafish seizure model. No antiproliferative activity was detected when tested on the cancer cell line HepG2, and no hepatotoxic effect was noted on normal liver cell line LO2.

Comprehensive analyses of solute carrier family members identify SLC12A2 as a novel therapy target for colorectal cancer.

As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What's more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.

Progress on the antiferromagnetic topological insulator MnBi2Te4.

Topological materials, which feature robust surface and/or edge states, have now been a research focus in condensed matter physics. They represent a new class of materials exhibiting nontrivial topological phases, and provide a platform for exploring exotic transport phenomena, such as the quantum anomalous Hall effect and the quantum spin Hall effect. Recently, magnetic topological materials have attracted considerable interests due to the possibility to study the interplay between topological and magnetic orders. In particular, the quantum anomalous Hall and axion insulator phases can be realized in topological insulators with magnetic order. MnBi2Te4, as the first intrinsic antiferromagnetic topological insulator discovered, allows the examination of existing theoretical predictions; it has been extensively studied, and many new discoveries have been made. Here we review the progress made on MnBi2Te4 from both experimental and theoretical aspects. The bulk crystal and magnetic structures are surveyed first, followed by a review of theoretical calculations and experimental probes on the band structure and surface states, and a discussion of various exotic phases that can be realized in MnBi2Te4. The properties of MnBi2Te4 thin films and the corresponding transport studies are then reviewed, with an emphasis on the edge state transport. Possible future research directions in this field are also discussed.

Layer Hall effect induced by hidden Berry curvature in antiferromagnetic insulators.

The layer Hall effect describes electrons spontaneously deflected to opposite sides at different layers, which has been experimentally reported in the MnBi2Te4 thin films under perpendicular electric fields. Here, we reveal a universal origin of the layer Hall effect in terms of the so-called hidden Berry curvature, as well as material design principles. Hence, it gives rise to zero Berry curvature in momentum space but non-zero layer-locked hidden Berry curvature in real space. We show that, compared to that of a trivial insulator, the layer Hall effect is significantly enhanced in antiferromagnetic topological insulators. Our universal picture provides a paradigm for revealing the hidden physics as a result of the interplay between the global and local symmetries, and can be generalized in various scenarios.

The CXCLs-CXCR2 axis modulates the cross-communication between tumor-associated neutrophils and tumor cells in cervical cancer.

OBJECTIVE: This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis. METHODS: Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies. RESULTS: Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in vitro and in vivo. CONCLUSIONS: The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.

Mitral valvuloplasty using real-time three-dimensional transesophageal echocardiography.

OBJECTIVE: This study aimed to investigate the structure of the mitral valve in patients undergoing mitral valvuloplasty (MVP) using real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). The main objective was to study the relationship between intraoperative annuloplasty ring size and mitral valve structure dimensions, with a focus on exploring the application value of RT-3D-TEE in MVP. METHODS: A total of 28 patients with degenerative mitral regurgitation (DMR), who underwent MVP between February and September 2022, as well as 12 normal control cases, were enrolled in this study. The MV annulus and leaflets were quantitatively analyzed using MVN software. RESULTS: The DMR group exhibited significantly greater dimensions in various parameters of the mitral valve, including the anterolateral-to-posteromedial diameter (DAlPm ), anterior-to-posterior diameter (DAP ), annulus height (HA ), three-dimensional annulus circumference (CA3D ), two-dimensional annulus area (AA2D ), anterior leaflet area (Aant ), posterior leaflet area (Apost ), anterior leaflet length (Lant ), posterior leaflet length (Lpost ), and tenting volume (Vtent ) compared to the control group. CONCLUSION: Real-time three-dimensional transesophageal echocardiography provides valuable insights into the morphological structure of the mitral valve and lesion location. It can aid in surgical decision-making, validate the success of MVP, and potentially reduce mortality and complications associated with mitral valve repair procedures.

Chlamydospore dormancy and predatory activity of nematophagous fungus Duddingtonia flagrans.

The chlamydospores of Duddingtonia flagrans are an essential survival and reproductive structure and also an effective ingredient for the biocontrol of parasitic nematodes in livestock. In this study, entering and exiting dormancy conditions and predatory activity of the fungal chlamydospores were conducted. During this fungal growth process, the cultivation time is negatively correlated with spore germination rates. After the spores were processed by vacuum drying for 168 h, their germination rate dropped to 0.94%. In contrast, the percentage of living spores remained 54.82%, suggesting that the spores entered structural dormancy in the arid environment. Meanwhile, the efficacies of the spore against Haemonchus contortus larvae were 93.05% (0 h), 92.19% (16 h), 92.77% (96 h), and 86.45% (168 h), respectively. After dormant spores were stored at 4°C, -20°C, and 28°C (RH90 ~ 95%) for 7 days, their germination rate began to increase significantly (p < 0.05). For in vitro predation assay under the condition of 28°C (RH90 ~ 95%), the predation rate was significantly higher on the 7th day after incubation than that on the 3rd day (p < 0.05). During the period when spores were stored at room temperature for 8 months, their germination rate decreased in the first 5 months and then increased slowly to reach a peak in the 7th month. However, the reduction rate of H. contortus L3 in feces captured by spores remained above 71% for the first 7 months. These results will help us increase the end products yield and the quality of biological control of parasitic nematodes in livestock.

Combined untargeted and targeted lipidomics approaches reveal potential biomarkers in type 2 diabetes mellitus cynomolgus monkeys.

BACKGROUND: The significantly increasing incidence of type 2 diabetes mellitus (T2DM) over the last few decades triggers the demands of T2DM animal models to explore the pathogenesis, prevention, and therapy of the disease. The altered lipid metabolism may play an important role in the pathogenesis and progression of T2DM. However, the characterization of molecular lipid species in fasting serum related to T2DM cynomolgus monkeys is still underrecognized. METHODS: Untargeted and targeted LC-mass spectrometry (MS)/MS-based lipidomics approaches were applied to characterize and compare the fasting serum lipidomic profiles of T2DM cynomolgus monkeys and the healthy controls. RESULTS: Multivariate analysis revealed that 196 and 64 lipid molecules differentially expressed in serum samples using untargeted and targeted lipidomics as the comparison between the disease group and healthy group, respectively. Furthermore, the comparative analysis of differential serum lipid metabolites obtained by untargeted and targeted lipidomics approaches, four common serum lipid species (phosphatidylcholine [18:0_22:4], lysophosphatidylcholine [14:0], phosphatidylethanolamine [PE] [16:1_18:2], and PE [18:0_22:4]) were identified as potential biomarkers and all of which were found to be downregulated. By analyzing the metabolic pathway, glycerophospholipid metabolism was associated with the pathogenesis of T2DM cynomolgus monkeys. CONCLUSION: The study found that four downregulated serum lipid species could serve as novel potential biomarkers of T2DM cynomolgus monkeys. Glycerophospholipid metabolism was filtered out as the potential therapeutic target pathway of T2DM progression. Our results showed that the identified biomarkers may offer a novel tool for tracking disease progression and response to therapeutic interventions.

Sesquiterpenoids from aged Artemisia argyi and their 3D-QSAR for anti-HBV activity.

Artemisia argyi Levl. Et Vant, commonly known as "Chinese Mugwort," has been utilized in traditional Chinese medicine and cuisine for centuries. Aged Chinese Mugwort has been uncovered to possess superior quality and safety, and its ethyl acetate extract has been found to exhibit anti-hepatitis B virus (HBV) activity. In this study, twenty-five sesquiterpenoids were isolated and characterized from three-year-aged A. argyi. Among them, 14 previously undescribed sesquiterpenoids (1-14), featuring double bond oxidation or ring opening. It is hypothesized that during the aging process, sesquiterpenes undergo oxidative transformation of their double bonds to form alcohols due to external factors and inherent properties. The anti-HBV activity and cytotoxicity of all compounds were assessed in vitro using HepG 2.2.15 cells, and their structure-activity relationships were analyzed through three-dimensional quantitative structure-activity relationship (3D-QASR) techniques. The α-methylene-γ-lactone sesquiterpenoid derivatives were discovered to have potent inhibitory activity against HBV. This research may broaden the potential applications of Chinese Mugwort and offer further guidance for its development and utilization as functional food or traditional Chinese medicine.

[Research progress in pharmacotherapy of insomnia].

Insomnia is extremely common and is a risk factor for a variety of physical and psychological disorders in addition to contributing to the reduced quality of life of patients and the burden of healthcare costs. Although cognitive behavioral therapy is the first-line treatment for insomnia, its difficulty of access and high cost have hindered its application. Therefore, pharmacotherapy remains the common treatment choice for patients and clinicians. Existing chemical drugs including benzodiazepine receptor agonists, dual orexin receptor antagonists, melatonin and its receptor agonists, histamine antagonists, antidepressants, and antipsychotics are able to induce and/or maintain sleep and have good therapeutic effects on acute insomnia, but their efficacy on chronic insomnia is indefinite. Furthermore, they have several side effects and affect sleep structure and physiological function. Under the guiding principle of holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has shown a good effect in clinical practice, but with little high-grade clinical evidence. The mechanism, dose, half-life period, adjustment of sleep structure, and side effects of hypnotic drugs are key factors to be considered for clinical use. This paper analyzed and summarized the drugs for insomnia from the above aspects, and is expected to provide references for the application and development of sedative and hypnotic drugs.

Broad and colossal edge supercurrent in Dirac semimetal Cd3As2 Josephson junctions.

Edge supercurrent has attracted great interest recently due to its crucial role in achieving and manipulating topological superconducting states. Proximity-induced superconductivity has been realized in quantum Hall and quantum spin Hall edge states, as well as in higher-order topological hinge states. Non-Hermitian skin effect, the aggregation of non-Bloch eigenstates at open boundaries, promises an abnormal edge channel. Here we report the observation of broad edge supercurrent in Dirac semimetal Cd3As2-based Josephson junctions. The as-grown Cd3As2 nanoplates are electron-doped by intrinsic defects, which enhance the non-Hermitian perturbations. The superconducting quantum interference indicates edge supercurrent with a width of ~1.6 µm and a magnitude of ~1 µA at 10 mK. The wide and large edge supercurrent is inaccessible for a conventional edge system and suggests the presence of non-Hermitian skin effect. A supercurrent nonlocality is also observed. The interplay between band topology and non-Hermiticity is beneficial for exploiting exotic topological matter.

CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway.

CXCL8-CXCR1/CXCR2 signaling pathways might form complex crosstalk among different cell types within the ovarian tumor microenvironment, thereby modulating the behaviors of different cells. This study aimed to investigate the expression pattern of CXCL8 in the ovarian tumor microenvironment and its impact on both endothelial-to-mesenchymal transition (EndMT) and ferroptosis of endothelial cells. The human monocytic cell line THP-1 and the human umbilical vein endothelial cell line PUMC-HUVEC-T1 were used to conduct in vitro studies. Erastin was used to induce ferroptosis. Results showed that tumor-associated macrophages are the major source of CXCL8 in the tumor microenvironment. CXCL8 treatment promoted the nucleus entrance of NF-κB p65 and p65 phosphorylation via CXCR2 in endothelial cells, suggesting activated NF-κB signaling. Via the NF-κB signaling pathway, CXCL8 enhanced TGF-ß1-induced EndMT of PUMC-HUVEC-T1 cells and elevated their expression of SLC7A11 and GPX4. These trends were drastically weakened in groups with CXCR2 knockdown or SB225002 treatment. TPCA-1 reversed CXCL8-induced upregulation of SLC7A11 and GPX4. CXCL8 protected endothelial cells from erastin-induced ferroptosis. However, these protective effects were largely canceled when CXCR2 was knocked down. In summary, CXCL8 can activate the NF-κB signaling pathway in endothelial cells in a CXCR2-dependent manner. The CXCL8-CXCR2/NF-κB axis can enhance EndMT and activate SLC7A11 and GPX4 expression, protecting endothelial cells from ferroptosis.

Giant nonlocal edge conduction in the axion insulator state of MnBi2Te4.

The recently discovered antiferromagnetic (AFM) topological insulator (TI) MnBi2Te4 represents a versatile material platform for exploring exotic topological quantum phenomena in nanoscale devices. It has been proposed that even-septuple-layer (even-SL) MnBi2Te4 can host helical hinge currents with unique nonlocal behavior, but experimental confirmation is still lacking. In this work, we report transport studies of exfoliated MnBi2Te4 flakes with varied thicknesses down to the few-nanometer regime. We observe giant nonlocal transport signals in even-SL devices when the system is in the axion insulator state but vanishingly small nonlocal signal in the odd-SL devices at the same magnetic field range. In conjunction with theoretical calculations, we demonstrate that the nonlocal transport is via the helical edge currents mainly distributed at the hinges between the side and top/bottom surfaces. The helical edge currents in the axion insulator state may find unique applications in topological quantum devices.