Comparative efficacy and safety of six angiotensin II receptor blockers in hypertensive patients: a network meta-analysis.

BACKGROUND: The antihypertensive effects of angiotensin II receptor blockers (ARBs) are well recognized. However, conventional meta-analyses have reported inconsistent results on their efficacy and safety. AIM: This study aimed to evaluate the efficacy and safety of six ARBs (losartan, valsartan, irbesartan, telmisartan, candesartan, and olmesartan) commonly used to treat hypertension, using a network meta-analysis. METHOD: We retrieved randomized controlled trials on hypertension treatment using ARBs from the PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases. The efficacy outcomes included absolute changes in office systolic and diastolic blood pressure from baseline, and 24-h ambulatory blood pressure. Safety outcomes were assessed by the total number of adverse events (AEs) during treatment. We conducted the network meta-analysis using the 'bugsnet' and 'gemtc' packages in R. RESULTS: A total of 193 studies were included. Olmesartan had the highest surface under the cumulative ranking in reducing office systolic (91.4%) and diastolic blood pressure (87.2%). Candesartan has the highest ranking in lowering 24 h ambulatory systolic blood pressure (95.4%), while telmisartan reduced 24 h ambulatory diastolic blood pressure (83.4%). Olmesartan also ranked highest in safety (70.8%). CONCLUSION: Valsartan and losartan were less effective in lowering blood pressure than other drugs, with no significant differences. Olmesartan and telmisartan were associated with fewer AEs than losartan, although the incidence of adverse events was similar between the other blockers. Olmesartan and telmisartan demonstrated the best balance of antihypertensive efficacy and minimal adverse events. More research is needed to confirm whether telmisartan and olmesartan are optimal choices for controlling blood pressure in patients.

Anatomy of Hidden Dzyaloshinskii-Moriya Interactions and Topological Spin Textures in Centrosymmetric Crystals.

The Dzyaloshinskii-Moriya interaction (DMI) is understood to be forbidden by the symmetry of centrosymmetric systems, thus restricting the candidate types for investigating many correlated physical phenomena. Here, we report the hidden DMI existing in centrosymmetric magnets driven by the local inversion symmetry breaking of specific spin sublattices. The opposite DMI spatially localized on the inverse spin sublattice favors the separated spin spiral with opposite chirality. Furthermore, we elucidate that hidden DMI widely exists in many potential candidates, from the first-principles calculations on the mature crystal database. Interestingly, novel topological spin configurations, such as the anti-chirality-locked merons and antiferromagnetic-ferromagnetic meron chains, are stabilized as a consequence of hidden DMI. Our understanding enables the effective control of DMI by symmetry operations at the atomic level and enlarges the range of currently useful magnets for topological magnetism.

Above-room-temperature chiral skyrmion lattice and Dzyaloshinskii-Moriya interaction in a van der Waals ferromagnet Fe3-xGaTe2.

Skyrmions in existing 2D van der Waals (vdW) materials have primarily been limited to cryogenic temperatures, and the underlying physical mechanism of the Dzyaloshinskii-Moriya interaction (DMI), a crucial ingredient for stabilizing chiral skyrmions, remains inadequately explored. Here, we report the observation of Néel-type skyrmions in a vdW ferromagnet Fe3-xGaTe2 above room temperature. Contrary to previous assumptions of centrosymmetry in Fe3-xGaTe2, the atomic-resolution scanning transmission electron microscopy reveals that the off-centered FeΙΙ atoms break the spatial inversion symmetry, rendering it a polar metal. First-principles calculations further elucidate that the DMI primarily stems from the Te sublayers through the Fert-Lévy mechanism. Remarkably, the chiral skyrmion lattice in Fe3-xGaTe2 can persist up to 330 K at zero magnetic field, demonstrating superior thermal stability compared to other known skyrmion vdW magnets. This work provides valuable insights into skyrmionics and presents promising prospects for 2D material-based skyrmion devices operating beyond room temperature.

Cistanche phenylethanoid glycosides induce apoptosis and pyroptosis in T-cell lymphoma.

Cistanche deserticola, known for its extensive history in Traditional Chinese Medicine (TCM), is valued for its therapeutic properties. Recent studies have identified its anticancer capabilities, yet the mechanisms underlying these properties remain to be fully elucidated. In this study, we determined that a mixture of four cistanche-derived phenylethanoid glycosides (CPhGs), echinacoside, acteoside, 2-acetylacteoside, and cistanoside A, which are among the main bioactive compounds in C. deserticola, eliminated T-cell lymphoma (TCL) cells by inducing apoptosis and pyroptosis in vitro and attenuated tumor growth in vivo in a xenograft mouse model. At the molecular level, these CPhGs elevated P53 by inhibiting the SIRT2-MDM2/P300 and PI3K/AKT carcinogenic axes and activating PTEN-Bax tumor-suppressing signaling. Moreover, CPhGs activated noncanonical and alternative pathways to trigger pyroptosis. Interestingly, CPhGs did not activate canonical NLRP3-caspase-1 pyroptotic signaling pathway; instead, CPhGs suppressed the inflammasome factor NLRP3 and the maturation of IL-1ß. Treatment with a caspase-1/4 inhibitor and silencing of Gasdermin D (GSDMD) or Gasdermin E (GSDME) partially rescued CPhG-induced cell death. Conversely, forced expression of NLRP3 restored cell proliferation. In summary, our results indicate that CPhGs modulate multiple signaling pathways to achieve their anticancer properties and perform dual roles in pyroptosis and NLRP3-driven proliferation. This study offers experimental support for the potential application of CPhGs in the treatment of TCL.

Long-term survival in a patient with multiple metastatic gastric cancer treated with PTX plus emvolimab and disitamab vedotin: case report and treatment experience: A case report.

RATIONALE: Most Chinese patients with locally advanced gastric cancer at diagnosis have an overall 5-year survival rate of <50%. Surgical resection alone is not suitable for patients with locally advanced gastric cancer. Currently, comprehensive treatment is the focus of locally advanced gastric cancer. PATIENTS CONCERNS: The patient, a 56-year-old female, was admitted to the hospital because of "4 + months of double hydronephrosis found during a physical examination." Who was admitted for computer tomography and gastroscopy examinations, and take pathological tissue specimens during endoscopic examination. DIAGNOSES: Computed tomography assessment indicated ulcerative gastric cancer with an abdominal implant, bladder, and bone metastases. An endoscopic examination revealed that the ulcer of the gastric angle was huge, and through relevant auxiliary examinations, the diagnosis of this disease is gastric cancer complicated with multiple metastases to bladder, rectum, lumbar spine, and peritoneum. Clinically diagnosed as cT4bN3M1. INTERVENTIONS: The patient is currently undergoing first, second, and third line neoadjuvant therapy, combined with immunotherapy, targeted therapy, neoadjuvant intraperitoneal systemic chemotherapy, nutritional support, and other treatment plans. OUTCOMES: After 15 cycles of treatment, the progression-free survival had reached 15 months. The patient had an NRS2002 score of 1, an ECOG score of I, a quality of life score of 55, albumin of 35.27 g/L, and a decrease in abdominal and pelvic fluid accumulation and exudation compared to before. LESSONS: We demonstrated high survival of almost 3 years in a patient with gastric cancer that was complicated by bone, peritoneal, rectal, and bladder metastases. The combination of immunotherapy, targeted therapy, and neoadjuvant intraperitoneal systemic chemotherapy, along with the maintenance of nutritional status and CTCs could be a valuable modality for the subsequent treatment and observation of similar patients.

Impact of macrophage differentiation on hematopoietic function enhancement by Shenzhu ErKang Syrup.

Shenzhu Erkang Syrup (SZEK) is a traditional Chinese medicine that improves spleen and stomach function, tonifying the Qi and activating the blood; however, its therapeutic effects in hematopoietic dysfunction and their underlying mechanism remain unexplored. In this study, mice were given cyclophosphamide (100 mg/kg) by intraperitoneal injections for three days to produce hematopoietic dysfunction model. We investigated the hematopoietic effect and mechanism of SZEK in mice with hematopoietic dysfunction via histopathological examination, flow cytometry, enzyme-linked immunosorbent assay, and Western blotting combined with intestinal flora and serum metabolomics analysis. In mice with hematopoietic dysfunction, SZEK (gavage, 0.3 mL/25 g) alleviated pathological damage to the bone marrow and spleen; increased the number of naïve cells (Lin-), hematopoietic stem cells (Lin-Sca-1+c-Kit+), long-term self-renewing hematopoietic stem cells (Lin-Sca-1+c-Kit+CD48-CD150+), B lymphocytes (CD45+CD19+), and macrophages (CD11b+F4/80+) in the bone marrow; and reduced inflammation. Preliminary intestinal flora and serum metabolome analyses indicated that the pro-hematopoietic mechanism of SZEK was associated with macrophage differentiation. Further validation revealed that SZEK promoted hematopoiesis by decreasing the number of M2 macrophages and inhibiting the secretion of negative hematopoietic regulatory factors in mice with hematopoietic dysfunction.

Large and tunable magnetoresistance in van der Waals ferromagnet/semiconductor junctions.

Magnetic tunnel junctions (MTJs) with conventional bulk ferromagnets separated by a nonmagnetic insulating layer are key building blocks in spintronics for magnetic sensors and memory. A radically different approach of using atomically-thin van der Waals (vdW) materials in MTJs is expected to boost their figure of merit, the tunneling magnetoresistance (TMR), while relaxing the lattice-matching requirements from the epitaxial growth and supporting high-quality integration of dissimilar materials with atomically-sharp interfaces. We report TMR up to 192% at 10 K in all-vdW Fe3GeTe2/GaSe/Fe3GeTe2 MTJs. Remarkably, instead of the usual insulating spacer, this large TMR is realized with a vdW semiconductor GaSe. Integration of semiconductors into the MTJs offers energy-band-tunability, bias dependence, magnetic proximity effects, and spin-dependent optical-selection rules. We demonstrate that not only the magnitude of the TMR is tuned by the semiconductor thickness but also the TMR sign can be reversed by varying the bias voltages, enabling modulation of highly spin-polarized carriers in vdW semiconductors.

Ruderman-Kittel-Kasuya-Yosida-Type Interlayer Dzyaloshinskii-Moriya Interaction in Synthetic Magnets.

Conduction electron spins interacting with magnetic impurity spins can mediate an interlayer exchange interaction, namely, the Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction. This discovery opened the way to significant technological developments in the field of magnetic storage and spintronics. So far, the RKKY-type interlayer interaction has been found to construct symmetric coupling of magnetism; however, the asymmetric counterpart remains unexplored. Here we report unprecedented RKKY-type interlayer Dzyaloshinskii-Moriya interaction (DMI) in synthetic magnets, exhibiting a damped oscillatory feature. This asymmetric interlayer interaction is found to be dramatically dependent on the intermediate coupling layer. By introducing the Fert-Lévy model to the trilayer system, we reveal that the in-plane inversion symmetry breaking plays a pivotal role for generating interlayer DMI and the RKKY oscillation is an intrinsic behavior in metallic multilayers. Our finding fills up the empty block for RKKY-type asymmetric interlayer exchange coupling in comparison to the well-known (symmetric) RKKY-type interlayer exchange coupling.

Proximity-Induced Interfacial Room-Temperature Ferromagnetism in Semiconducting Fe3GeTe2.

The discoveries of two-dimensional ferromagnetism and magnetic semiconductors highly enrich the magnetic material family for constructing spin-based electronic devices, but with an acknowledged challenge that the Curie temperature (Tc) is usually far below room temperature. Many efforts such as voltage control and magnetic ion doping are currently underway to enhance the functional temperature, in which the involvement of additional electrodes or extra magnetic ions limits their application in practical devices. Here we demonstrate that the magnetic proximity, a robust effect but with elusive mechanisms, can induce room-temperature ferromagnetism at the interface between sputtered Pt and semiconducting Fe3GeTe2, both of which do not show ferromagnetism at 300 K. The independent electrical and magnetization measurements, structure analysis, and control samples with Ta highlighting the role of Pt confirm that the ferromagnetism with the Tc of above 400 K arises from the Fe3GeTe2/Pt interfaces, rather than Fe aggregation or other artificial effects. Moreover, contrary to conventional ferromagnet/Pt structures, the spin current generated by the Pt layer is enhanced more than two times at the Fe3GeTe2/Pt interfaces, indicating the potential applications of the unique proximity effect in building highly efficient spintronic devices. These results may pave a new avenue to create room-temperature functional spin devices based on low-Tc materials and provide clear evidence of magnetic proximity effects by using nonferromagnetic materials.

Intrinsic Atomic-Scale Antiferroelectric VOF3 Nanowire with Ultrahigh-Energy Storage Properties.

Antiferroelectrics with antiparallel dipoles are receiving tremendous attention for their technological importance and fundamental interest. However, intrinsic one-dimensional (1D) materials harboring antiferroelectric ordering have rarely been reported despite the promise of novel paradigms for miniaturized and high-density electronics. Herein, based on first- and second-principles calculations, we demonstrate the VOF3 atomic wire, exfoliated from an experimentally synthesized yet underexplored 1D van der Waals (vdW) bulk, as a new 1D antiferroelectric material. The energetic, thermal, and dynamic stabilities of the nanowire are confirmed theoretically. Moreover, the temperature-dependent phase transitions and double-hysteresis polarization-field loops are computed for the VOF3 nanowire by constructing the second-principles model. According to the hysteresis loops, high energy densities and efficiencies can be obtained simultaneously at room temperature in the VOF3 nanowire under moderate applied fields. Our identified 1D atomic wire not only expands the family of antiferroelectricity but also holds potential for novel high-power energy storage nanodevices.

Deterministic Magnetization Switching via Tunable Noncollinear Spin Configurations in Canted Magnets.

Spin obit torque (SOT) driven magnetization switching has been used widely for encoding consumption-efficient memory and logic. However, symmetry breaking under a magnetic field is required to realize the deterministic switching in synthetic antiferromagnets with perpendicular magnetic anisotropy (PMA), which limits their potential applications. Herein, we report all electric-controlled magnetization switching in the antiferromagnetic Co/Ir/Co trilayers with vertical magnetic imbalance. Besides, the switching polarity could be reversed by optimizing the Ir thickness. By using the polarized neutron reflection (PNR) measurements, the canted noncollinear spin configuration was observed in Co/Ir/Co trilayers, which results from the competition of magnetic inhomogeneity. In addition, the asymmetric domain walls demonstrated by micromagnetic simulations result from introducing imbalance magnetism, leading to the deterministic magnetization switching in Co/Ir/Co trilayers. Our findings highlight a promising route to electric-controlled magnetism via tunable spin configuration, improve our understanding of physical mechanisms, and significantly promote industrial applications in spintronic devices.

Direct Observation of Magnetic Skyrmions and Their Current-Induced Dynamics in Epitaxial Single-Crystal Oxide Films.

Magnetic skyrmions are scarcely investigated for single-crystal quality films, for which skyrmions may have a remarkable performance. Even in the limited studies in this aspect, the skyrmions are usually probed by the topological Hall effect, missing important information on dynamic properties. Here, we present a comprehensive investigation on the generation/manipulation of magnetic skyrmions in La0.67Ba0.33MnO3 single-crystal films. Using the technique of magnetic force microscopy, the current-driven skyrmion dynamics are directly observed. Unlike isolated skyrmions produced by magnetic field alone, closely packed skyrmions can be generated by electric pulses in a magnetic background, with a high density (∼60/µm2) and a small size (dozens of nanometers). The threshold current moving skyrmions is ∼2.3 × 104 A/cm2, 2-3 orders of magnitude lower than that required by metallic multilayers or van der Waals ferromagnetic heterostructures. Our work demonstrates the great potential of single-crystal oxide films in developing skyrmion-based devices.

Best treatment options for occult breast cancer: A meta-analysis.

Objectives: Occult breast cancer (OBC) is a rare malignant breast tumor. Because of the rare cases and limited clinical experience, a huge therapeutic difference has existed all over the world and standardized treatments have yet been established. Methods: A meta-analysis was conducted using MEDLINE and Embase databases to identify the choice of OBC surgical procedures in all studies: (1) patients undergoing axillary lymph node dissection (ALND) or sentinel lymph node biopsy (SLNB) only; (2) patients undergoing ALND with radiotherapy (RT); (3) patients undergoing ALND with breast surgery (BS); (4) patients undergoing ALND with RT and BS; and (5) patients undergoing observation or RT only. The primary endpoints were mortality rates, the second endpoints were distant metastasis and locoregional recurrence. Results: Among the 3,476 patients, 493 (14.2%) undergo ALND or SLNB only; 632 (18.2%) undergo ALND with RT; 1483 (42.7%) undergo ALND with BS; 467 (13.4%) undergo ALND RT and BS, and 401 (11.5%) undergo observation or RT only. After comparing the multiple groups, both groups 1 and 3 have higher mortality rates than group 4 (30.7% vs. 18.6%, p < 0.0001; 25.1% vs. 18.6%, p = 0.007), and group 1 has higher mortality rates than groups 2 and 3 (30.7% vs.14.7%, p < 0.00001; 30.7 vs. 19.4%, p < 0.0001). Group (1 + 3) had a prognosis advantage over group 5 (21.4% vs. 31.0%, p < 0.00001). There was no significant difference both in the distant recurrence rates and locoregional rates between group (1 + 3) and group (2 + 4) (21.0% vs. 9.7%, p = 0.06; 12.3% vs. 6.5%, p = 0.26). Conclusion: On the basis of this meta-analysis, our study indicates that BS including modified radical mastectomy (MRM) and breast-conserving surgery (BCS) combined RT may appear as the optimal surgical approach in patients with OBC. RT cannot prolong both the time of distant metastasis and the local recurrences.

Hole doping induced ferromagnetism and Dzyaloshinskii-Moriya interaction in the two-dimensional group-IVA oxides.

Based on the first-principles calculations, we examine the effect of hole doping on the ferromagnetism and Dzyaloshinskii-Moriya interaction (DMI) for PbSnO2, SnO2and GeO2monolayers. The nonmagnetic to ferromagnetic transition and the DMI can emerge simultaneously in the three two-dimensional IVA oxides. By increasing the hole doping concentration, we find the ferromagnetism can be strengthened for the three oxides. Due to different inversion symmetry breaking, isotropic DMI is found in PbSnO2, whereas anisotropic DMI presents in SnO2and GeO2. More appealingly, for PbSnO2with different hole concentrations, DMI can induce a variety of topological spin textures. Interestingly, a peculiar feature of synchronously switch of magnetic easy axis and DMI chirality upon hole doping is found in PbSnO2. Hence, Néel-type skyrmions can be tailored via changing hole density in PbSnO2. Furthermore, we demonstrate that both SnO2and GeO2.with different hole concentrations can host antiskyrmions or antibimerons (in-plane antiskyrmions). Our findings demonstrate the presence and tunability of topological chiral structures in p-type magnets and open up new possibility for spintronics.

The involvement of Th1 cell differentiation in the anti-tumor effect of purified polysaccharide from Sanghuangporus vaninii in colorectal cancer via multi-omics analysis.

Sanghuangporus vaninii is a medicinal mushroom, which has been used as a treatment for various diseases; however, the therapeutic potential and mechanism of action of S. vaninii in colorectal cancer (CRC) remain unknown. Herein, human colon adenocarcinoma cells were used to analyze the anti-CRC effects of the purified polysaccharide of S. vaninii (SVP-A-1) in vitro. In SVP-A-1-treated B6/JGpt-Apcem1Cin (Min)/Gpt male (ApcMin/+) mice, 16S rRNA sequencing was performed on cecal feces, metabolites were examined in serum, and LC-MS/MS protein detection was performed in colorectal tumors. Protein changes were further confirmed by various biochemical detection methods. Water-soluble SVP-A-1 with a molecular weight of 22.5 kDa was first obtained. SVP-A-1 prevented gut microbiota dysbiosis related to metabolic pathways of L-arginine biosynthesis, increased L-citrulline levels in the serum of ApcMin/+ mice, mediated L-arginine synthesis, and improved antigen presentation in dendritic cells and activated CD4+ T cells; the resulting Th1 cells released IFN-γ and TNF-α to act on tumor cells and promoted the sensitivity of tumor cells to cytotoxic T lymphocytes. In summary, SVP-A-1 exerted anti-CRC effects and has excellent potential for CRC treatment.

Effect of CO2-Brine-Rock Interactions on the Pore Structure of the Tight Sandstone during CO2 Flooding: A Case Study of Chang 7 Member of the Triassic Yanchang Formation in the Ordos Basin, China.

CO2 flooding is an effective technique to enhance oil recovery from tight sandstone reservoirs. The CO2-rich fluid reacts with the in situ minerals and results in the corrosion and precipitation of minerals in the sandstone, affecting the connectivity and morphological features of pores. However, the diagenesis of the tight sandstone is complex, and the structural modification behavior and mechanism in different lithofacies of tight sandstone during CO2 flooding are still unclear. This study combined CO2 flooding, thin-section casting, scanning electron microscopy, nuclear magnetic resonance, X-ray diffraction, and fractal analysis methods to investigate the changes in the pore structure of tight sandstone after CO2 flooding. The results show that the cement of the tight sandstone is complex and diverse. The tight sandstone can be divided into two types of lithofacies: clay cementation (CL) and ferrocalcite cementation (CA). The mineralogical alterations occur differently in each lithofacies of tight sandstone. Alterations in the cement minerals affect the pores morphology of tight sandstone depending on their mineralogical structure and texture, and the CO2 flooding mainly changes the micromorphology and heterogeneity of large pores. Clay minerals dominate the cement in the CL lithofacies of tight sandstone. The dissolution mainly occurs in small pores because the precipitation of new minerals and exfoliation of skeleton particles partially block large pores and transform them into small pores. Thus, the number of small pores of CL lithofacies increases while the number of large pores decreases. Such a phenomenon hinders the increase in porosity and permeability. On the other side, in the CA lithofacies of tight sandstone, the cement is dominated by ferrocalcite, and the dissolution of ferrocalcite is the primary mechanism of mineralogical alteration. As the ferrocalcite dissolution expands, it creates new flow paths, improving the connectivity of pores. The petrophysical properties of CA lithofacies improve significantly after CO2 flooding. There is a crucial need to study the changes in diagenetic characteristics of tight sandstone due to CO2 flooding. Such type of study provides insights related to the improvement and evaluation of the development of tight sandstone reservoirs during CO2 flooding.

Voltage-Controlled Dzyaloshinskii-Moriya Interaction Torque Switching of Perpendicular Magnetization.

Magnetization switching is the most important operation in spintronic devices. In modern nonvolatile magnetic random-access memory (MRAM), it is usually realized by spin-transfer torque (STT) or spin-orbit torque (SOT). However, both STT and SOT MRAM require current to drive magnetization switching, which will cause Joule heating. Here, we report an alternative mechanism, Dzyaloshinskii-Moriya interaction (DMI) torque, that can realize magnetization switching fully controlled by voltage pulses. We find that a consequential voltage-controlled reversal of DMI chirality in multiferroics can lead to continued expansion of a skyrmion thanks to the DMI torque. Enough DMI torque will eventually make the skyrmion burst into a quasiuniform ferromagnetic state with reversed magnetization, thus realizing the switching of a perpendicular magnet. The discovery is demonstrated in two-dimensional multiferroics, CuCrP_{2}Se_{6} and CrN, using first-principles calculations and micromagnetic simulations. As an example, we applied the DMI torque for simulating leaky-integrate-fire functionality of biological neurons. Our discovery of DMI torque switching of perpendicular magnetization provides tremendous potential toward magnetic-field-free and current-free spintronic devices, and neuromorphic computing as well.

Gradient-Induced Dzyaloshinskii-Moriya Interaction.

The Dzyaloshinskii-Moriya interaction (DMI) that arises in the magnetic systems with broken inversion symmetry plays an essential role in topological spintronics. Here, by means of atomistic spin calculations, we study an intriguing type of DMI (g-DMI) that emerges in the films with composition gradient. We show that both the strength and chirality of g-DMI can be controlled by the composition gradient even in the disordered system. The layer-resolved analysis of g-DMI unveils its additive nature inside the bulk layers and clarifies the linear thickness dependence of g-DMI observed in experiments. Furthermore, we demonstrate the g-DMI-induced chiral magnetic structures, such as spin spirals and skyrmions, and the g-DMI driven field-free spin-orbit torque (SOT) switching, both of which are crucial toward practical device application. These results elucidate the underlying mechanisms of g-DMI and open up a new way to engineer the topological magnetic textures.